反应详情

Oxalyl chloride (0.043 mL, 0.5 mmol) was added to a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the product of Step D) (200 mg, 0.66 mmol) and two drops of N,N-dimethylformamide (DMF) in 30 mL of methylene chloride at room temperature and the reaction was stirred for 10 minutes. After this time a catalytic amount of 4-(dimethylamino)pyridine was added, followed by dropwise addition of a mixture of triethylamine (184 mL, 1.4 mmol) and 2-bromo-4,6-difluoroaniline in 10 mL of methylene chloride. The reaction was stirred overnight and then concentrated to near dryness. Chromatography on silica gel with hexane/ethyl acetate gradient as eluent (9:1 to 1:1) afforded an oil. The oil was then cooled in dry ice and triturated with ether/hexane to provide the title compound (0.22 g), a compound of the present invention, as a solid melting at 138-139° C.

1. stirringThe reaction was stirred overnight
2. concentrationconcentrated
3. customChromatography on silica gel with hexane/ethyl acetate gradient as eluent (9:1 to 1:1) afforded an oil
4. customtriturated with ether/hexane